Image credit: Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings

I really love the paper Assumption-Free Estimation of Heritability from Genome-Wide Identity-by-Descent Sharing between Full Siblings. I first read it about six years ago. The result is rather straightforward, but the problem is empirically a moderately deep one. Modern analytic genetics as the fusion between Mendelism and biometrics began with R. A. Fisher’s The Correlation between Relatives on the Supposition of Mendelian Inheritance in 1918. But note, that paper assumed particular relatedness between relatives. As highlighted in the above paper the expected values for most categories of relatedness always had a variance component which was unaccounted for, and so reduced the power of the methodology to ascertain the extent of heritability. The relatedness you can expect between any two siblings is ~0.50, and that is also the average across all siblings. But the reality is that in most cases two given siblings will not share half their genes identical by descent.

Before the genomic era the precise assessment of relatedness in a given case was laborious, if at all feasible. But not so today. Because modern genomics is anthropocentric we can focus first on humans. Because I’ve had my whole family genotyped I know the relatedness between pairs where you have an expected value which is not likely a realized value (siblings, uncles & aunts to nieces and nephews, and grandparents to grandchildren). So, I know that my daughter has a relatedness of 0.22 to my mother and 0.28 to my father, and not 0.25. I also know that my relatedness to my siblings is 0.52, 0.51, and 0.48. Or that two of my siblings are 0.41 related!

Why does this matter? When it comes to the cliché “nature vs. nurture” argument siblings are powerful and clear evidence. On the one hand you have the people who make maximal claims for the environment controlling variation within the population. And on the other hand you have the other element which didn’t see a gene-trait correlation which it didn’t like. Siblings comparisons are powerful because the design here is not opaque or abstruse, but totally transparent. Siblings share the same home environment.* If they are near in age they also share similar socioeconomic parameters. And yet they vary. Why? In a large cohort of siblings you obtain a range of genetic variation as in the figure above. A simple test of whether genetic components are powerful would be to examine the patterns across siblings. In other words, are siblings who differ in final trait values those siblings who tend to differ in genetic relatedness?

This would also get at some correlations which people observe on the population scale. For example, are taller people more intelligent than shorter people because of correlations between the genes for height and intelligence? This observation has been offered up on the comments of this weblog by uncritical people innumerable times. But a simple answer is at hand for the curious: the correlation does not persist across siblings, who vary a great deal in height (a highly heritable trait) and intelligence, but not in a correlated fashion. Instead of constantly looking at population scale correlations, which are subject to specious and legitimate critiques, we could instead look at patterns which occur within families. This will not silence all skeptics, nor should it. But it will be a big step forward in making the “nature vs. nurture” question more tractable for the general public.

Finally, how are we going to do this? Much of this will no doubt occur in the academy or through organized institutions. But there is absolutely no reason that the general public couldn’t “crowd source” this sort of project. openSNP already exists, and many scientific genetics obsessives like me have already genotyped our whole families. In the near future a critical mass will exist to explore a whole range of questions, just by looking at the incredible genetic variation within families.

* The proliferation of half-siblings and foster-parenthood in the lower middle to lower class segments of the United States is a potentially vast “natural experiment” for a future behavior genomicist.

Quote: “I also know that my relatedness to my siblings is 0.52, 0.51, and 0.48.”

Do these differences in relatedness reflect any differences in your relationships with your siblings? I know the differences are small but I wonder if people can instinctively tell which siblings they are most similar to genetically and whether this knowledge is reflected in their relationships with those siblings.

Miley Cyrax

Is there a correlation between sibling genomic similarity and the closeness of their height? What about genomic similarity and closeness of their IQ?

JL

Miley, regarding height, read the paper Razib linked to at the start of his post. As to IQ, I don’t think this research design has yet been applied to it.

Superfast Jellyfish

According to 23andme I share 49.9% of my genes with my mother and 47.3% with my father. Is it possible to have numbers that fall a few percentage points short of 100%, or is this just random error?

Karl Zimmerman

4 –

I’d hazard a guess this is because you don’t share an X chromosome with your father (presuming you’re male) and you don’t share a Y chromosome with your mother.

Superfast Jellyfish

#5–Right, but shouldn’t the maternal sharing and paternal sharing add up to be about 100% instead of 97.2%? And on a related note, is the maternal component going to be slightly larger in men since the X chromosome is bigger than the Y?

https://plus.google.com/109962494182694679780/posts Razib Khan

#1, that’s a hypothesis. not been tested yet. though note that i’m concerned more about average effects over many cohorts of siblings. don’t expect much in 48 vs. 52 ibd.

#2, quantitative traits should reflect total genome content. i’ve blogged this before at length; you’re a long time reader, you should read me closer. there was a recent paper using genomic relatedness and IQ I believe. please google visscher, dreary, etc. not siblings though.

And on a related note, is the maternal component going to be slightly larger in men since the X chromosome is bigger than the Y?

i think that’s what’s going on. there’s not as much stuff on the Y. i don’t even know if it’s added into the computation? i just focus on the autosomes for that reason.

http://dispatchesfromturtleisland.blogspot.com ohwilleke

“Siblings share the same home environment.”

In case of many traits, from personality to sexual orientation, birth order is a non-shared component of the otherwise shared environnment of siblings that may have material effects.

Of course, these issues are not present in the same way for fraternal twins.

Half-siblings pose much more useful natural experiements than foster parenting situations, since almost all foster parenting situations involve a fairly extended and almost always acutely negative period of environmental exposure at a developmentally critical time period in a genetic parent family before the foster parenting period begins. This is not true to nearly the same extent in half-sibling situations.

Within the universe of half siblings, cases in which war widows remarry and have new children might be particularly instructive as there is no selection bias in the sample for people who had poor marriages to start with that could have been a negative environmental impact on the older sibling.

https://plus.google.com/109962494182694679780/posts Razib Khan

since almost all foster parenting situations involve a fairly extended and almost always acutely negative period of environmental exposure at a developmentally critical time period in a genetic parent family before the foster parenting period begins.

as unpleasant as it is to consider, if the environment is relatively uniform in a negative fashion that may be informative of the nature of response in variation across individuals of different genetic backgrounds.

http://dispatchesfromturtleisland.blogspot.com ohwilleke

“if the environment is relatively uniform in a negative fashion that may be informative of the nature of response in variation across individuals of different genetic backgrounds.”

Alas, Anna Karenina is on point here. While posititive environments may all be similar to each other, negative environments can be negative in a multitude of individual ways. There are probably a dozen common reasons that children are removed from their homes and the environmental effects associated with each one vary. Unless you can sort based on reason for termination of parental rights (which is often legally suppressed by juvenile justice system rules), there are potentially signficant and hard to discern environmental exposure biases present.

https://plus.google.com/109962494182694679780/posts Razib Khan

dude, maybe. but you should stop talking like you are a behavior geneticist. at least to me 😉

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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at http://www.razib.com